This invention relates to a chemically modified bilirubin oxidase, and more specifically, to a bilirubin oxidase derivative resulting from chemical modification of bilirubin oxidase with a water-soluble polymeric substance.
The chemically modified bilirubin oxidase provided by this invention is useful as a drug for treating jaundice because it acts to specifically decompose and remove bilirubin which abnormally increases in blood in jaundice, and has very high stability in blood.
Jaundice is a condition in which bilirubin in blood increases abnormally to yellow the skin, mucous membranes and other tissues. Jaundice accompanying various hepatic diseases involves strong cytotoxin of bilirubin, and often brings about serious results (see Maisels, M. J.: Neonatology, edited by Avery, G. B., Lippicott Co., Philadelphia, 1981, pages 473-544). Thus, neonatal jaundice is treated by light therapy or therapy by exchange transfusion (see Cohen, A. V. and Ostrow, J. D.: Pediatrics, 65: 740-750, 1980). Extracorporeal therapies have also been attempted. For example, bilirubin in blood is adsorbed on various resins (see Scharschmidt, B. F. et al.: J. Clin. Invest., 53: 786-795, 1974), or decomposed and removed by using bilirubin oxidase fixed to a carrier such as a polysaccharide (e.g., cellulose, dextran or agarose), polyacrylamide gel, porous glass and polystyrene (see Labin, A. et al.: Science, 230: 543-545, 1985).
The above therapeutic methods have some difficulties such as a low therapeutic efficiency, securing of transfusion preparations, the non-specificity of adsorbing components and the complexity of operation.
To remove bilirubin in blood from jaundice patients, the use of bilirubin oxidase is excellent in view of its reaction specificity. So far, the in vivo administration of the bilirubin oxidase has been impossible because of its extremely poor stability in vivo and its antigenicity.